Altiok E, Minarovits J, Hu L F, Contreras-Brodin B, Klein G, Ernberg I
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):905-9. doi: 10.1073/pnas.89.3.905.
Epstein-Barr virus nuclear antigens (EBNAs) are expressed in a cell-phenotype-dependent manner. EBNA 1 is regularly expressed in all Epstein-Barr virus-carrying cells, whereas EBNAs 2-6 are only expressed in Epstein-Barr virus-carrying cells with a lymphoblastoid phenotype including group III Burkitt lymphoma (BL) lines positive for B-cell activation markers. Transcripts are initiated at the BCR2 or exceptionally at one BWR1 promoter in lymphoblastoid cell lines and group III BL lines. In group I BL lines, nasopharyngeal carcinoma, and the somatic cell hybrids, where EBNAs 2-6 are downregulated, the BCR2/BWR1 promoter complex is inactive or switched off. Upregulation of EBNAs 2-6 in group III BL cells and in 5-azacytidine-treated group I BL cells accompanies the activation of the silent BCR2/BWR1 promoters. Activation of BCR2 parallels demethylation of at least one CpG pair in the same promoter region. The activity of BCR2/BWR1 promoter complex depends on a particular B-cell phenotype. EBNA 1 transcription must be initiated at another promoter in cells that express only EBNA 1.
爱泼斯坦-巴尔病毒核抗原（EBNAs）以细胞表型依赖的方式表达。EBNA 1在所有携带爱泼斯坦-巴尔病毒的细胞中持续表达，而EBNAs 2 - 6仅在具有淋巴母细胞样表型的携带爱泼斯坦-巴尔病毒的细胞中表达，包括对B细胞活化标志物呈阳性的III组伯基特淋巴瘤（BL）细胞系。转录在淋巴母细胞系和III组BL细胞系中的BCR2或极少数情况下在一个BWR1启动子处起始。在I组BL细胞系、鼻咽癌和体细胞杂种中，EBNAs 2 - 6下调，BCR2/BWR1启动子复合体无活性或被关闭。III组BL细胞和经5 - 氮杂胞苷处理的I组BL细胞中EBNAs 2 - 6的上调伴随着沉默的BCR2/BWR1启动子的激活。BCR2的激活与同一启动子区域中至少一对CpG的去甲基化平行。BCR2/BWR1启动子复合体的活性取决于特定的B细胞表型。在仅表达EBNA 1的细胞中，EBNA 1转录必须在另一个启动子处起始。
